TNF and cholestasis: For example, in a bile duct ligation-induced murine cholestasis model, the reciprocal interaction of hepatic NK cells and Kupffer cells stimulates IL-6 production from the latter and this results in ameliorated cholestatic liver injury.32 In another study, NK cell-derived IFN-γ and Kupffer cell-derived proinflammatory cytokines, such as TNF-α, IL-12 and IL-18, act synergistically to mediate acute liver injury.29 NK cells are also capable of regulating M1/M2 polarization of Kupffer cells, promoting M1-like polarization while suppressing M2-like polarization through secreting IFN-γ.